A41.0
Conditions
Interventions
Group 1: Experimental: Orally administered antibiotic
First choice (MRSA and MSSA): trimethoprim-sulfamethoxazole, or Second choice (MSSA): clindamycin, or Second choice (MRSA): linezolid
administere
Sponsors
Universitätsklinikum Düsseldorf i.A. der Heinrich-Heine-Universität
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: •Age at least 18 years •Not legally incapacitated •Written informed consent from the trial subject has been obtained •Blood culture positive for S. aureus not considered to represent contamination •At least one negative follow-up blood culture obtained within 24-96 hours after the start of adequate antimicrobial therapy to rule out persistent bacteremia and absence of a blood culture positive for S. aureus at the same time or thereafter. •Five to seven full days of appropriate i.v. antimicrobial therapy administered prior to randomization documented in the patient chart. Appropriate therapy has all of the following characteristics: oAntimicrobial therapy has to be initiated within 72h after the first positive blood culture was drawn. oProvided in-vitro susceptibility and adequate dosing (as judged by the principle investigator) preferred agents for pre-randomization antimicrobial therapy are: flucloxacillin, cloxacillin, vancomycin, and daptomycin. However, the following parenteral antimicrobials are allowed: oMSSA: penicillinase-resistant penicillins (e.g. flucloxacillin, cloxacillin), ß-lactam plus ß-lactamase-inhibitors (e.g. ampicillin+sulbactam, piperacillin+tazobactam), cephalosporins (except ceftazidime), carbapenems, clindamycin, fluoroquinolones, trimethoprim-sulfamethoxazole, doxycycline, tigecycline, vancomycin, teicoplanin, telavancin, linezolid, daptomycin, ceftaroline, ceftobiprole, and macrolides. oMRSA: vancomycin, teicoplanin, telavancin, fluoroquinolones, clindamycin, trimethoprim-sulfamethoxazole, doxycycline, tigecycline, linezolid, daptomycin, macrolides, ceftaroline, and ceftobiprole.
Exclusion criteria
Exclusion criteria: •Polymicrobial bloodstream infection, defined as isolation of pathogens other than S. aureus from a blood culture obtained in the time from two days prior to the first positive blood culture with S. aureus until randomization. Common skin contaminants (coagulase-negative staphylococci, diphteroids, Bacillus spp., and Propionibacterium spp.) detected in one of several blood cultures will not be considered to represent polymicrobial infection •Recent history (within 3 months) of prior S. aureus bloodstream infection •In vitro resistance of S. aureus to all oral or all i.v. study drugs •Contraindications in reference document for all oral or all i.v. study drugs •Previously planned treatment with active drug against S. aureus during intervention phase (e.g. cotrimoxazol prohylaxis) •Signs and symptoms of complicated SAB as judged by an ID physician. Complicated infection is defined as at least one of the following: odeep-seated focus: e.g. endocarditis, pneumonia, undrained abscess, empyema, and osteomyelitis oseptic shock, as defined by the AACP criteria (23), within 4 days before randomization oprolonged bacteremia: positive follow-up blood culture more than 72h after the start of adequate antimicrobial therapy obody temperature >38 °C on two separate days within 48h before randomization •Presence of the following non-removable foreign bodies (if not removed 2 days or more before randomization): oprosthetic heart valve odeep-seated vascular graft with foreign material (e.g. PTFE or dacron graft). Hemodialysis shunts are not considered deep-seated vascular grafts (s. below). oventriculo-atrial shunt •Presence of a prosthetic joint (if not removed 2 days or more before randomization). This is not an exclusion criterion, if all of the following conditions are fulfilled: oprosthetic joint was implanted at least 6 months prior, and ocatheter-related infection, skin and soft tissue infection, or surgical wound infection is present (as defined below), and ojoint infection unlikely (no clinical or imaging signs) •Presence of a pacemaker or an automated implantable cardioverter defibrillator (AICD) device (if not removed 2 days or more before randomization). This is not an exclusion criterion, if all of the following conditions are fulfilled: o pacemaker or AICD was implanted at least 6 months prior, and ocatheter-related infection, skin and soft tissue infection, or surgical wound infection is present (as defined below), and ono clinical signs of infective endocarditis, and oinfective endocarditis unlikely by echocardiography (preferably TEE), and opocket infection unlikely (no clinical or imaging signs) •Failure to remove any intravascular catheter which was present when first positive blood culture was drawn within 4 days of the first positive blood culture •Severe liver disease. This is not an exclusion criterion, if the following condition is fulfilled: o catheter-related infection, skin and soft tissue infection, or surgical wound infection is present (as defined below) •End-stage renal disease. This is not an exclusion criterion, if all of the following conditions are fulfilled: ocatheter-related infection, skin and soft tissue infection, or surgical wound infection is present (as defined below), and ono clinical signs of infective endocarditis, and oinfective endocarditis unlikely by echocardiography (preferably TEE), and oin patients with a hemodialysis shunt with a non-removable foreign
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| - SAB-related complications (relapsing SAB, deep-seated infection with S. aureus, or attributable mortality) within 90 days | — |
Secondary
| Measure | Time frame |
|---|---|
| - Length of hospital stay Other variables: - 14, 30, and 90-day survival - Complications of intravenous therapy | — |
Countries
France, Germany, Netherlands, Spain
Contacts
Public ContactAchim Kaasch
Institut für Medizinische Mikrobiologie und Krankenhaushygiene
Outcome results
None listed